Density phase separation device

ABSTRACT

A mechanical separator for separating a fluid sample into first and second phases within a collection container is disclosed. The mechanical separator may have a separator body having a through-hole defined therein, with the through-hole adapted for allowing fluid to pass therethrough. The separator body includes a float, having a first density, and a ballast, having a second density greater than the first density. A portion of the float is connected to a portion of the ballast. Optionally, the float may include a first extended tab adjacent a first opening of the through-hole and a second extended tab adjacent the second opening of the through-hole. In certain configurations, the separator body also includes an extended tab band disposed about an outer surface of the float. The separator body may also include an engagement band circumferentially disposed about at least a portion of the separator body.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/888,238, filed Feb. 5, 2018, entitled “Density Phase SeparationDevice”, which is a divisional of U.S. application Ser. No. 14/572,102,filed Dec. 16, 2014, entitled “Density Phase Separation Device”, nowU.S. Pat. No. 9,919,307, which is a continuation of U.S. applicationSer. No. 12/780,432, filed May 14, 2010, entitled “Density PhaseSeparation Device”, now U.S. Pat. No. 8,998,000, which claims priorityto U.S. Provisional Patent Application Ser. No. 61/178,599 filed May 15,2009, the entire disclosures of each of which are hereby incorporated byreference.

BACKGROUND OF THE INVENTION Field of the Invention

The subject invention relates to a device for separating higher andlower density fractions of a fluid sample. More particularly, thisinvention relates to a device for collecting and transporting fluidsamples whereby the device and fluid sample are subjected tocentrifugation in order to cause separation of the higher densityfraction from the lower density fraction of the fluid sample.

Description of Related Art

Diagnostic tests may require separation of a patient's whole bloodsample into components, such as serum or plasma (the lower density phasecomponents), and red blood cells (the higher density phase components).Samples of whole blood are typically collected by venipuncture through acannula or needle attached to a syringe or an evacuated blood collectiontube. After collection, separation of the blood into serum or plasma andred blood cells is accomplished by rotation of the syringe or tube in acentrifuge. In order to maintain the separation, a barrier must bepositioned between the higher density and lower density phasecomponents. This allows the separated components to be subsequentlyexamined.

A variety of separation barriers have been used in collection devices todivide the area between the higher density and lower density phases of afluid sample. The most widely used devices include thixotropic gelmaterials, such as polyester gels. However, current polyester gel serumseparation tubes require special manufacturing equipment to both preparethe gel and fill the tubes. Moreover, the shelf-life of the gel-basedseparator product is limited. Over time, globules may be released fromthe gel mass and enter one or both of the separated phase components.Furthermore, commercially available gel barriers may react chemicallywith the analytes. Accordingly, if certain drugs are present in theblood sample when it is taken, an adverse chemical reaction with the gelinterface can occur. Furthermore, if an instrument probe is inserted toodeeply into a collection container, then the instrument probe may becomeclogged if it contacts the gel.

Certain mechanical separators have also been proposed in which amechanical barrier can be employed between the higher and lower densityphases of the fluid sample. Conventional mechanical barriers arepositioned between higher and lower density phase components utilizingelevated gravitational forces applied during centrifugation. For properorientation with respect to plasma and serum specimens, conventionalmechanical separators are typically positioned above the collected wholeblood specimen prior to centrifugation. This typically requires that themechanical separator be affixed to the underside of the tube closure insuch a manner that blood fill occurs through or around the device whenengaged with a blood collection set or phlebotomy needle. Thisattachment is required to prevent the premature movement of theseparator during shipment, handling, and blood draw. Conventionalmechanical separators are typically affixed to the tube closure by amechanical interlock between the bellows component and the closure.

Conventional mechanical separators have some significant drawbacks. Asshown in FIG. 1, conventional separators include a bellows 34 forproviding a seal with the tube or syringe wall 38. Typically, at least aportion of the bellows 34 is housed within, or in contact with a closure32. As shown in FIG. 1, as the needle 30 enters through the closure 32,the bellows 34 is depressed. This creates a void 36 in which blood maypool during insertion or removal of the needle. This can result insample pooling under the closure, device pre-launch in which themechanical separator prematurely releases during blood collection,trapping of a significant quantity of fluid phases, such as serum andplasma, poor sample quality, and/or barrier failure under certaincircumstances. Furthermore, previous mechanical separators are costlyand complicated to manufacture due to the complicated multi-partfabrication techniques.

Accordingly, a need exists for a separator device that is compatiblewith standard sampling equipment and reduces or eliminates theaforementioned problems of conventional separators. A need also existsfor a separator device that is easily used to separate a blood sample,minimizes cross-contamination of the higher and lower density phases ofthe sample during centrifugation, is independent of temperature duringstorage and shipping, and is stable to radiation sterilization. A needfurther exists for a unitary separation device that requires fewerrelative moving parts and that allows for enhanced ease of introducing aspecimen into a collection container.

SUMMARY OF THE INVENTION

The present invention is directed to an assembly for separating a fluidsample into a higher density and a lower density phase. Desirably, themechanical separator of the present invention may be used with acollection container, such as a tube, and is structured to move withinthe tube under the action of applied centrifugal force in order toseparate the portions of a fluid sample. In certain configurations, thetube is a specimen collection tube including an open end, a closed end,and a sidewall extending between the open end and closed end. Thesidewall includes an outer surface and an inner surface and the tubefurther includes a closure disposed to fit in the open end of the tubewith a resealable septum. Alternatively, both ends of the tube may beopen, and both ends of the tube may be sealed by elastomeric closures.At least one of the closures of the tube may include a needle pierceableresealable septum.

The mechanical separator may be disposed within the tube at a locationbetween the top closure and the bottom of the tube. The components ofthe separator are dimensioned and configured to achieve an overalldensity for the separator that lies between the densities of the phasesof a fluid sample, such as the higher and lower density phases of ablood sample.

In accordance with an embodiment of the present invention, a mechanicalseparator for separating a fluid sample into first and second phaseswithin a collection container includes a separator body having athrough-hole defined therein. The through-hole is adapted for allowingfluid to pass therethrough. The separator body includes a float, havinga first density, and a ballast, having a second density greater than thefirst density. A portion of the float is connected to a portion of theballast.

The mechanical separator may have a spheroid shape. Optionally, thefloat may include an exterior surface and a joining surface, and theballast may include a contact surface connected to the joining surfaceof the float and an exterior surface. The exterior surface of the floatand the exterior surface of the ballast taken together may form thespheroid shape.

In certain configurations, the float defines the through-hole adaptedfor allowing fluid to pass therethrough. The through-hole may have acircular cross-section. In other configurations, the through-hole mayhave an elliptical cross-section. The through-hole may be defined alonga through-axis, and the float may be adapted for deformation in adirection perpendicular to the through-axis upon applied rotationalforce.

In another configuration, the float further includes a first extendedtab adjacent a first opening of the through-hole and a second extendedtab adjacent the second opening of the through-hole. At least a portionof the first extended tab and at least a portion of the second extendedtab may be provided above and about the through-hole and extend radiallyoutwardly from the float in a direction parallel to the through-axis ofthe separator body. Optionally, the first extended tab, an upper surfaceof the float, and the second extended tab may form a convex upper floatsurface.

In another configuration, the separator body further includes anextended tab band disposed about a portion of an outer surface of thefloat. Optionally, a first portion of the extended tab band is disposedadjacent a first opening of the through-hole, and a second portion ofthe extended tab band is disposed adjacent a second opening of thethrough-hole. In a further configuration, at least one of the firstportion and the second portion of the extended tab band have a concavedownwardly-directed orientation. Optionally, at least one of the firstportion and the second portion of the extended tab band are oriented inan outwardly-extending arcuate shape about an upper portion of at leastone of the first opening and second opening of the through-hole. Atleast one of the first portion and the second portion of the extendedtab band may extend outwardly from the float in a direction parallel tothe through-axis. At least a portion of the first extended portion andat least a portion of the second extended portion of the extended tabband may have the same shape and curvature. In certain configurations,the extended tab band may further include a joining portion disposedbetween and connecting the first extended portion and the secondextended portion disposed on each connecting side of the separator body.The first extended portion and the second extended portion of theextended tab band have a concave downwardly-directed orientation, andthe joining portions of the extended tab band have a concaveupwardly-directed orientation. In certain configurations, the float mayinclude the extended tab band. Optionally, the float and the extendedtab band may be formed of TPE and the ballast is formed of PET.

The mechanical separator may also include an initial engagement bandcircumferentially disposed about the separator body. The initialengagement band may be continuous or at least partially segmented. Theinitial engagement band and the float may be formed of the samematerial. The initial engagement band may bisect at least a portion ofthe ballast.

In another configuration, the ballast may include a base portion and ajoining structure for engaging a portion of the float. The joiningstructure may include a plurality of arms for engaging a portion of thefloat, and the joining structure may provide flexure between the floatand the ballast. Optionally, at least a portion of the float may have acircular outer perimeter having a curved cross-section perpendicular tothe through-hole. In certain configurations, the float may include ajoining structure for engaging a portion of the ballast. The joiningstructure may include a plurality of arms for engaging a portion of theballast, and the joining structure may provide flexure between the floatand the ballast.

In accordance with another embodiment of the present invention, aseparation assembly for enabling separation of a fluid sample into firstand second phases includes a collection container having a first end, asecond end, and a sidewall extending therebetween. The collectioncontainer defines a longitudinal axis between the first end and thesecond end. The separation assembly further includes a mechanicalseparator having a separator body having a through-hole defined therein.The separator body is adapted to transition from a first initialposition in which the through-hole is oriented in an open position forallowing fluid to pass therethrough, to a second sealing position inwhich the through-hole is oriented in a closed position for preventingfluid from being received therethrough, upon applied rotational force.

In one configuration, the separation assembly further includes a closureadapted for sealing engagement with the first end of the collectioncontainer, with the mechanical separator releasably engaged with aportion of the closure. The mechanical separator may be engaged with aportion of the closure in the first initial position, and the mechanicalseparator may be engaged with a portion of the sidewall of thecollection container in the second sealing position. The closure mayinclude an engagement boss disposed within a portion of the through-holewhen the separator body is in the first initial position for forming afluid seal between a portion of the separator body and the closure.Optionally, at least a portion of the through-hole of the mechanicalseparator is oriented along the longitudinal axis of the collectioncontainer in the first initial position, and the through-hole isoriented perpendicular to the longitudinal axis of the collectioncontainer in the second sealing position. Transition of the through-holefrom the open position to the closed position may coincide with rotationof the mechanical separator from the first initial position to thesecond sealing position. The mechanical separator may sealingly engage aportion of the collection container wall in the second sealing positionto prevent flow of fluid therethrough or therearound.

In certain configurations, the separator body further includes a firstextended tab adjacent a first opening of the through-hole and a secondextended tab adjacent the second opening of the through-hole. The firstextended tab and the second extended tab may engage a portion of thesidewall of the collection container in the second sealing position. Inother configurations, the separator body further includes an extendedtab band disposed about a portion of an outer surface of the float. Theextended tab band may engage a portion of the sidewall of the collectioncontainer in the second sealing position, and the extended tab band mayform a continuous seal with the sidewall of the collection container inthe second sealing position.

In other configurations, the ballast includes a joining structure forengaging a portion of the float, and at least a portion of the floatincludes a circular outer perimeter having a curved cross-sectionperpendicular to the through-hole. The outer perimeter of the float mayform a continuous seal with the sidewall of the collection container inthe second sealing position. Optionally, the float includes a joiningstructure for engaging a portion of the ballast, and at least a portionof the float includes a circular outer perimeter having a curvedcross-section perpendicular to the through-hole, with the outerperimeter of the float forming a continuous seal with the sidewall ofthe collection container in the second sealing position.

In accordance with another embodiment of the present invention, aseparation assembly for enabling separation of a fluid sample into firstand second phases includes a collection container having a first end, asecond end, and a sidewall extending therebetween. The separationassembly further includes a mechanical separator having a separator bodyhaving a through-hole defined therein. The separator body includes afirst sealing perimeter for providing sealing engagement with a firstportion of a collection container while allowing a sample to passthrough the through-hole into the collection container, and a secondsealing perimeter for providing sealing engagement with a second portionof the collection container while maintaining a barrier for separationbetween the first and second phases.

The separation assembly may include a closure adapted for sealingengagement with the open end of the collection container, in which themechanical separator is releasably engaged with a portion of theclosure.

In accordance with another embodiment of the present invention, aseparation assembly for enabling separation of a fluid sample into firstand second phases includes a collection container having an open end, aclosed end, and a sidewall extending therebetween defining an interior.The collection container further defines a longitudinal axis between theopen end and the closed end. The separation assembly further includes aclosure adapted for sealing engagement with the open end of thecollection container, and a post engaged with the closure and adaptedfor positioning within the interior of the collection container. Thepost includes a post through-hole aligned along the longitudinal axis ofthe collection container. The separation assembly also includes amechanical separator releasably engaged with the post. The mechanicalseparator includes a separator body having a through-hole definedtherein along a through-axis, with the through-hole adapted for allowingfluid to pass therethrough. The separator body includes a float, havinga first density, and a ballast, having a second density greater than thefirst density. A portion of the float is connected to a portion of theballast, and a portion of the post is received within the through-holeof the separator forming a fluid path through the post and themechanical separator in an initial first position.

The separator body may further include an initial engagement bandcircumferentially disposed about a portion of the separator body. Theinitial engagement band and the float may be formed of the samematerial, and the initial engagement band may bisect at least a portionof the ballast. Optionally, the separator body is adapted to transitionfrom a first initial position in which a portion of the post is disposedwithin the through-hole and the separator body is oriented in an openposition for allowing fluid to pass therethrough, to a second sealingposition in which the separator body is disengaged from the post and thethrough-hole is oriented in a closed position for preventing fluid frombeing received therethrough, upon applied rotational force. Transitionof the separator body from the open position to the closed position mayinclude an axial movement of the separator body to disengage from thepost, and a rotational movement of the separator body from an initialfirst position to a second sealing position.

In accordance with yet another embodiment of the present invention, aseparation assembly for enabling separation of a fluid sample into firstand second phases includes a collection container having an open end, aclosed end, and a sidewall extending therebetween defining an interior.The collection container further defines a longitudinal axis between theopen end and the closed end. The separation assembly further includes aclosure adapted for sealing engagement with the open end of thecollection container. The closure includes a receiving end forpositioning within the open end of the collection container, with thereceiving end defining an interior cavity and including an undercutprotrusion extending into the interior cavity. The separation assemblyfurther includes a mechanical separator releasably engaged with theclosure. The mechanical separator includes a separator body having athrough-hole defined therein along a through-axis, with the through-holeadapted for allowing fluid to pass therethrough. The separator bodyincludes a float, having a first density, and a ballast, having a seconddensity greater than the first density, with a portion of the floatconnected to a portion of the ballast. The undercut protrusion of theclosure may be disposed within the through-hole of the separator, and atleast a portion of the separator body may be disposed within theinterior cavity of the closure in an initial first position.

In accordance with yet another embodiment of the present invention, acollection container includes a first region having an open top end anda first sidewall defining a first interior and a first exterior. Thecollection container also includes a second region having a closedbottom end and a second sidewall defining a second interior and a secondexterior. The first region and the second region may be aligned along alongitudinal axis such that the first interior and the second interiorare provided in fluid communication. A diameter of the first interiormay be greater than a diameter of the second interior, and at least onefluid flute may extend between the first region and the second region toallow passage of fluid therethrough from the first region to the secondregion.

In certain configurations, the first exterior has a 16 mm profile andthe second exterior has a 13 mm profile. The first interior may bedimensioned to accommodate a mechanical separator therein, and thesecond interior may be dimensioned to at least partially restrain aportion of the mechanical separator from passing therein absent appliedrotational force.

In accordance with yet another embodiment of the present invention, aseparation assembly for enabling separation of a fluid sample into firstand second phases includes a collection container having a first regionhaving an open top end and a first sidewall defining a first interiorand a first exterior, and a second region having a closed bottom end anda second sidewall defining a second interior and a second exterior. Thefirst region and the second region may be aligned along a longitudinalaxis such that the first interior and the second interior are providedin fluid communication, with a diameter of the first interior beinggreater than a diameter of the second interior. The separation assemblyfurther includes at least one fluid flute extending between the firstregion and the second region to allow passage of fluid therethrough fromthe first region to the second region. The separation assembly may alsoinclude a mechanical separator having a float, having a first density,and a ballast, having a second density greater than the first density,with a portion of the float connected to a portion of the ballast. Atleast a portion of the mechanical separator is prevented from enteringthe second region in an initial first position, and the mechanicalseparator is transitioned into the second region upon application ofrotational force to a second sealing position.

The mechanical separator may include a separator body having athrough-hole defined therein and adapted for allowing fluid to passtherethrough.

In accordance with still a further embodiment of the present invention,a separation assembly for enabling separation of a fluid sample intofirst and second phases includes a collection container having a firstend, a second end, and a sidewall extending therebetween defining aninterior. The separation assembly further includes a closure adapted forsealing engagement with the open end of the collection container. Theseparation assembly also includes a mechanical separator releasablyrestrained by at least one of the closure and the sidewall of thecollection container in an initial first position. The mechanicalseparator includes a separator body having a through-hole definedtherein along a through-axis, with the through-hole adapted for allowingfluid to pass therethrough. The separator body includes a float, havinga first density, and a ballast, having a second density greater than thefirst density, with a portion of the float connected to a portion of theballast. The separation assembly further includes a carrier releasablyengaged with a portion of the mechanical separator in the initialposition such that, upon application of rotational force, the separatorbody transitions from an initial position in which fluid may passthrough the through-hole, to a sealing position in which the mechanicalseparator prevents passage of fluid therethrough or therearound. Alsoupon application of rotational force, the carrier disengages from themechanical separator.

In still a further embodiment of the present invention, a separationassembly includes a separation assembly including a collection containerhaving a first end, a second end, and a sidewall extending therebetweendefining an interior. The separation assembly also includes a mechanicalseparator including a float and a ballast and capable of movement from afirst position to a sealing position. In the sealing position, a sealingperimeter is established between at least a portion of the interior andthe separator, the sealing perimeter having a varying position about aportion of the interior, with the varying position defining an averagesealing height. The mechanical separator also has a maximum height and aminimum height within the collection container, such that the averagesealing height is less than the maximum height minus the minimum height.

The assembly of the present invention is advantageous over existingseparation products that utilize separation gel. In particular, theassembly of the present invention will not interfere with analytes,whereas many gels interact with bodily fluids and/or analytes presentwithin a collection container. The assembly of the present invention isalso advantageous over existing mechanical separators in that theseparator does not require piercing of the separator body to introduce aspecimen into the collection container thereby minimizing pre-launch andsample pooling under the closure. The structure of the presentmechanical separator also minimizes the loss of trapped fluid phases,such as serum and plasma within the separator body. Additionally, theassembly of the present invention does not require complicated extrusiontechniques during fabrication, and may optimally employ two-shot moldingtechniques.

Further details and advantages of the invention will become clear fromthe following detailed description when read in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial cross-sectional side view of a conventionalmechanical separator.

FIG. 2 is a perspective view of a mechanical separator assembly having afloat defining a through-hole and a ballast in accordance with anembodiment of the present invention.

FIG. 3 is an alternative perspective view of the mechanical separatorassembly of FIG. 2.

FIG. 4 is a top view of the mechanical separator of FIG. 2.

FIG. 5 is a side view of the mechanical separator of FIG. 2.

FIG. 6 is a cross-sectional view of the mechanical separator of FIG. 2taken along line 6-6 of FIG. 5.

FIG. 7 is a front view of the mechanical separator of FIG. 2.

FIG. 8 is a cross-sectional view of the mechanical separator of FIG. 2taken along line 8-8 of FIG. 7.

FIG. 9 is a top view of an alternative mechanical separator having afloat defining a through-hole and a ballast, with first and secondextended tabs forming a substantially convex upper float surface inaccordance with an embodiment of the present invention.

FIG. 10 is a side view of the mechanical separator of FIG. 9.

FIG. 11 is a cross-sectional view of the mechanical separator of FIG. 9taken along line 11-11 of FIG. 10.

FIG. 12 is a front view of the mechanical separator of FIG. 9.

FIG. 13 is a cross-sectional view of the mechanical separator of FIG. 9taken along line 13-13 of FIG. 12.

FIG. 14 is a perspective view of an alternative mechanical separatorhaving a float defining an elliptical through-hole and a ballast inaccordance with an embodiment of the present invention.

FIG. 15 is an alternative perspective view of the mechanical separatorof FIG. 14.

FIG. 16 is a top view of the mechanical separator of FIG. 15.

FIG. 17 is a side view of the mechanical separator of FIG. 15.

FIG. 18 is a cross-sectional view of the mechanical separator of FIG. 15taken along line 18-18 of FIG. 17.

FIG. 19 is a front view of the mechanical separator of FIG. 15.

FIG. 20 is a cross-sectional view of the mechanical separator of FIG. 15taken along line 20-20 of FIG. 19.

FIG. 20A is a perspective view of a mechanical separator having aspheroid shaped body and a reduced separation between the first extendedtab and the second extended tab in accordance with an embodiment of thepresent invention.

FIG. 21 is a cross-sectional view of an alternative mechanical separatorhaving an elliptical interior taken along a similar cross-sectional lineas that shown in FIG. 18.

FIG. 22 is a partial perspective view of the mechanical separator havingan elliptical interior as shown in FIG. 21.

FIG. 23 is a cross-sectional view of an alternative mechanical separatorhaving an elliptical through-hole taken along a similar cross-sectionalline as that shown in FIG. 18.

FIG. 24 is a partial perspective view of the mechanical separator havingan elliptical through-hole as shown in FIG. 23.

FIG. 25 is a cross-sectional view of an alternative mechanical separatorhaving a substantially round interior and side-cuts taken along asimilar cross-sectional line as that shown in FIG. 18.

FIG. 26 is a partial perspective view of the mechanical separator havinga substantially round interior and side-cuts as shown in FIG. 25.

FIG. 27 is a partial cross-sectional side view of a mechanical separatorof the present invention affixed to a closure in accordance with anembodiment of the present invention.

FIG. 28 is a partial cross-sectional side view of a mechanical separatordisposed within a collection container in an initial position forallowing fluid to pass through the through-hole in accordance with anembodiment of the present invention.

FIG. 29 is a partial cross-sectional side view of a mechanical separatordisposed within a collection container as shown in FIG. 28 in a sealingposition for establishing a barrier between lighter and denser phaseswithin a collection container after application of rotational force inaccordance with an embodiment of the present invention.

FIG. 30 is a perspective view of a mechanical separator in accordancewith an embodiment of the present invention having a seal line forengagement with a collection container in an initial position.

FIG. 31 is a perspective view of the mechanical separator of FIG. 30having a seal line for engagement with a collection container in asealing position.

FIG. 31A is a perspective view of a mechanical separator having apartially scalloped surface in accordance with an embodiment of thepresent invention.

FIG. 31B is a front view of the mechanical separator of FIG. 31A.

FIG. 31C is a perspective view of a mechanical separator in accordancewith an embodiment of the present invention.

FIG. 31D is a top view of the mechanical separator of FIG. 31C.

FIG. 31E is a front view of the mechanical separator of FIG. 31C.

FIG. 31F is a cross-sectional view of the mechanical separator of FIG.31C taken along line 31F-31F of FIG. 31E.

FIG. 31G is a side view of the mechanical separator of FIG. 31C.

FIG. 31H is a cross-sectional view of the mechanical separator of FIG.31C taken along line 31H-31H of FIG. 31G.

FIG. 31I is a bottom view of the mechanical separator of FIG. 31C.

FIG. 32 is a perspective view of a mechanical separator having aninitial engagement band in accordance with an embodiment of the presentinvention.

FIG. 33 is an alternative perspective view of a mechanical separatorhaving an initial engagement band as shown in FIG. 32.

FIG. 34 is a side view of the mechanical separator having an initialengagement band as shown in FIG. 33.

FIG. 35 is a partial cross-sectional side view of the mechanicalseparator having an initial engagement band of FIG. 33 engaged with aportion of the sidewall of a collection container and closure inaccordance with an embodiment of the present invention.

FIG. 35A is a perspective view of a mechanical separator having anextended tab band in accordance with an embodiment of the presentinvention.

FIG. 35B is a left side view of the mechanical separator of FIG. 35A.

FIG. 35C is a front view of the mechanical separator of FIG. 35A.

FIG. 35C1 is a cross-sectional view of the mechanical separator of FIG.35A taken along line 35C1-35C1 of FIG. 35B.

FIG. 35D is a cross-sectional view of the mechanical separator of FIG.35A taken along line 35D-35D of FIG. 35C.

FIG. 35E is a perspective view of a mechanical separator having analternative extended tab band in accordance with an embodiment of thepresent invention.

FIG. 35F is a perspective view of a mechanical separator having ajoining structure in accordance with an embodiment of the presentinvention.

FIG. 35G is a front view of the mechanical separator of FIG. 35F.

FIG. 35H is a cross-sectional view of the mechanical separator of FIG.35G taken along line 35H-35H of FIG. 35F.

FIG. 35I is a top view of the mechanical separator of FIG. 35F.

FIG. 35J is a schematic front view of the mechanical separator of FIG.35F disposed within a collection container in various states of descentwithin the collection container in accordance with an embodiment of thepresent invention.

FIG. 35K is a schematic front view of the mechanical separator of FIG.35J in a sealing position in accordance with an embodiment of thepresent invention.

FIG. 35L is a perspective view of a mechanical separator having analternative joining structure in accordance with an embodiment of thepresent invention.

FIG. 35M is a front view of the mechanical separator of FIG. 35L.

FIG. 35N is a perspective view of a mechanical separator having analternative joining structure in accordance with an embodiment of thepresent invention.

FIG. 35O is a front view of the mechanical separator of FIG. 35N.

FIG. 36 is a partial cross-sectional side view of a mechanical separatorhaving a circuitous though-hole in an initial position in accordancewith an embodiment of the present invention.

FIG. 37 is a partial cross-sectional side view of the mechanicalseparator of FIG. 36 having a circuitous though-hole in a sealingposition in accordance with an embodiment of the present invention.

FIG. 38 is a representational cross-section of a mechanical separatorhaving a float and a ballast separated by a thermoplastic elastomersection defining a through-hole in an initial resting position inaccordance with yet another embodiment of the present invention.

FIG. 39 is a representational cross-section of the mechanical separatorof FIG. 38 having a float and a ballast separated by a thermoplasticelastomer section defining a through-hole in an activated positionduring application of rotational force.

FIG. 40 is a cross-sectional side view of a separation assembly having amechanical separator engaged with a portion of a collection containerhaving a closure engaged therewith in accordance with an embodiment ofthe present invention.

FIG. 41 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a post which isengaged with an undercut of closure in accordance with an embodiment ofthe present invention.

FIG. 42 is a partial cross-sectional perspective of the closure of FIG.41.

FIG. 43 is a perspective front view of the post of FIG. 41.

FIG. 44 is a perspective rear view of the post of FIG. 41.

FIG. 45 is a side view of a collection container having a first region,a second region, and a plurality of fluid flutes in accordance with anembodiment of the present invention.

FIG. 46 is a cross-sectional partial side view of a separation assemblyhaving a mechanical separator disposed within the collection containerof FIG. 45 in accordance with an embodiment of the present invention.

FIG. 46A is a cross-sectional side view of an alternative collectioncontainer for use with a mechanical separator in accordance with anembodiment of the present invention.

FIG. 47 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged within a portion of aclosure in accordance with an embodiment of the present invention.

FIG. 48 is a partial cross-sectional perspective of the closure of FIG.47.

FIG. 49 is a cross-sectional side view of a separation assembly having amechanical separator engaged with a closure having an engagement boss inaccordance with an embodiment of the present invention.

FIG. 50 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a closure having analternative engagement boss in accordance with an embodiment of thepresent invention.

FIG. 51 is a cross-sectional side view of the separation assembly ofFIG. 50 having a sealant disposed between a portion of the mechanicalseparator and a portion of the closure in accordance with an embodimentof the present invention.

FIG. 52 is a close-up sectional view of the sealant shown in FIG. 51.

FIG. 53 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a closure having analternative engagement boss in accordance with an embodiment of thepresent invention.

FIG. 54 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a closure having analternative engagement boss in accordance with an embodiment of thepresent invention.

FIG. 55 is a perspective view of the closure of FIG. 54 having anengagement boss including a plurality of depending feet.

FIG. 56 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a molding insert inaccordance with an embodiment of the present invention.

FIG. 57 is a perspective view of the molding insert of FIG. 56.

FIG. 58 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a molding insert inaccordance with an embodiment of the present invention.

FIG. 59 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a molding insert inaccordance with an embodiment of the present invention.

FIG. 60 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a carrier engagedwith a portion of the closure in accordance with an embodiment of thepresent invention.

FIG. 61 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with an alternativecarrier engaged with a portion of the closure in accordance with anembodiment of the present invention.

FIG. 62 is a perspective view of the carrier of FIG. 61.

FIG. 63 is a cross-sectional side view of a separation assembly having amechanical separator engaged with a carrier in an initial position inaccordance with an embodiment of the present invention.

FIG. 64 is a cross-sectional side view of the separation assembly ofFIG. 63 having a mechanical separator in a sealing position disengagedfrom the carrier after application of rotational force in accordancewith an embodiment of the present invention.

FIG. 65 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with an alternativecarrier in an initial position in accordance with an embodiment of thepresent invention.

FIG. 66 is a cross-sectional side view of the separation assembly ofFIG. 65 having a mechanical separator in a sealing position disengagedfrom the carrier after application of rotational force in accordancewith an embodiment of the present invention.

FIG. 67 is a cross-sectional side view of an alternative separationassembly having a mechanical separator engaged with a dissolvablecarrier in an initial position in accordance with an embodiment of thepresent invention.

FIG. 68 is a cross-sectional side view of the separation assembly ofFIG. 67 having a mechanical separator in a sealing position illustratingthe carrier in the fully dissolved state after application of rotationalforce in accordance with an embodiment of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

For purposes of the description hereinafter, the words “upper”, “lower”,“right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”,“longitudinal”, and like spatial terms, if used, shall relate to thedescribed embodiments as oriented in the drawing figures. However, it isto be understood that many alternative variations and embodiments may beassumed except where expressly specified to the contrary. It is also tobe understood that the specific devices and embodiments illustrated inthe accompanying drawings and described herein are simply exemplaryembodiments of the invention.

The mechanical separator of the present invention is intended for usewith a collection container for providing separation of a sample intohigher and lower density phase components, as will be discussed herein.For example, the present mechanical separator can be used to provide aseparation of serum or plasma from whole blood through the use ofdifferential buoyancy to cause a sealing area to contract when submergedin a specimen exposed to elevated gravitational forces through appliedrotational force or centrifugation. In one embodiment, the elevatedgravitational forces can be provided at a rate of at least 2,000revolutions/minute, such as at least 3,400 revolutions/minute.

Referring to FIGS. 2-8, the mechanical separator 40 of the presentinvention includes a separator body 41 including a float 42 and aballast 44 connected to the float 42. In one embodiment, the float 42has a first density and the ballast 44 has a second density, with thesecond density being greater than the first density. In anotherembodiment, the float 42 has a first buoyancy and the ballast 44 has asecond buoyancy, with the first buoyancy being greater than the secondbuoyancy. In one embodiment, it is desirable that the float 42 of themechanical separator 40 be made from a material having a density that islighter than the liquid or specimen intended to be separated into twophases. For example, if it is desired to separate human blood into serumand plasma, then it is desirable that the float 42 have a density of nomore than about 1.020 g/cc. In one configuration, the float 42 of themechanical separator 40 may be extruded and/or molded of a resilientlydeformable and self-sealable material, such as a thermoplastic elastomer(TPE). In yet another embodiment, the float 42 may be extruded and/ormolded of a resiliently deformable material that exhibits good sealingcharacteristics when contact is established with a collection container,as will be discussed herein. Maintenance of the float density within thespecified tolerances is more easily obtained by using a standardmaterial that does not require compounding with, for example, glassmicro-spheres in order to reduce the material density.

The mechanical separator 40 also includes a through-hole 46 definedtherein, such as along a through-axis T of the separator body 41. Asshown in FIGS. 3, 5, and 8, the through-hole 46 may extend through theentire separator body 41 and includes a first opening 48 and a secondopening 50 aligned along the through-axis T. In one configuration, thethrough-hole 46 bisects or substantially bisects the volumetric centerof the separator body 41. In one embodiment, the through-hole 46 isdisposed entirely within the float 42. In a further embodiment, thefloat 42 may further include a first extended tab 52 adjacent the firstopening 48 of the through-hole 46, and a second extended tab 54 adjacentthe second opening 50 of the through-hole 46. The first extended tab 52and/or the second extended tab 54 may be co-formed with the float 42,forming a portion of the float 42 itself. In another configuration, thefirst extended tab 52 and/or the second extended tab 54 may beseparately formed and subsequently joined with the float 42. The firstextended tab 52 and the second extended tab 54 may be provided above,such as substantially above, the through-axis T of the separator body41. The first extended tab 52 and the second extended tab 54 may also beprovided about, such as substantially about, a portion of thethrough-hole 46, such as in an outwardly-extending arcuate shape aboutan upper portion 56 of the through-hole 46. The first extended tab 52and the second extended tab 54 may extend outwardly from the float 42 ina direction parallel or substantially parallel to the through axis T ofthe separator body 41, such that the first extended tab 52 and thesecond extended tab 54 may have the same shape and curvature orsubstantially the same shape and curvature. In yet another embodiment,as shown in FIG. 8, the first extended tab 52 includes a first outermostedge 68 at the upper outermost portion of a first side of thethrough-hole 46, and the second extended tab 54 includes a secondoutermost edge 70 at the corresponding upper outermost portion of asecond side of the through-hole 46. In one configuration, the firstoutermost edge 68 extends outwardly a distance that is greater than thelower outermost portion 72 of the first side of the through-hole 46. Thesecond outermost edge 70 also extends outwardly a distance that isgreater than the corresponding lower outermost portion 74 of the secondside of the through-hole 46. Accordingly, the diameter Di of theseparator body 41 taken about the first extended tab 52 and the secondextended tab 54 about an upper portion of the through-hole 46 isslightly greater than the diameter D₂ of the separator body 41 takenabout the lower portion of the through-hole 46 defined by the loweroutermost portions 72, 74.

In one embodiment, the float 42 has an exterior surface 58 that isgenerally arcuate in shape, such as at least partially rounded orsubstantially rounded, and a joining surface 60, shown in FIGS. 6 and 8,adapted for engagement with a portion of the ballast 44. The ballast 44also includes an exterior surface 62 that is also generally arcuate inshape, such as at least partially rounded or substantially rounded, anda contact surface 64, also shown in FIGS. 6 and 8, that is adapted forjoining with the joining surface 60 of the float 42. In one embodiment,when taken together, the exterior surface 58 of the float 42 and theexterior surface 62 of the ballast 44 form a generally round exterior,such as a spheroid shape. It is understood herein that the term“spheroid shape” may include other configurations, in addition to aperfect sphere, that are aspects of the invention which may provideslightly non-uniform diameters taken through the mid-point. For example,different planes taken through the float 42 and ballast 44 which bisectthe midpoint of the mechanical separator 40 may have varying diameterand still give rise to a generally rounded or ball-like mechanicalseparator 40 having a spheroid shape. In one embodiment, the float 42and the ballast 44 may be separately formed and subsequently assembled.In another embodiment, the float 42 and the ballast 44 may be co-formed,such as co-extruded and/or co-molded, such as by a two-shot ormulti-shot molding process such that both components are integrallylinked together to form a complete separator body 41. In anotherconfiguration, this integral linkage between the float 42 and theballast 44 may be created by a material bond between the two components,by a mechanical interlock, or by a combination of a material bond and amechanical interlock. In addition, the float 42 and the ballast 44 maybe linked together by a separate post-molding operation, such asadhesive, heat-staking, and/or ultrasonic welding. As shown in FIGS. 6and 8, the ballast 44 may include an attachment protrusion 66 whichassists in the engagement of the ballast 44 and the float 42.

In one embodiment, it is desirable that the ballast 44 of the mechanicalseparator 40 be made from a material having a higher density than theliquid intended to be separated into two phases. For example, if it isdesired to separate human blood into serum and plasma, then it isdesirable that the ballast 44 have a density of at least 1.029 g/cc. Inone embodiment, the ballast 44 can be formed from mineral filledpolypropylene. It is anticipated herein that both the float 42 and theballast 44 could be formed of various other materials with sufficientbiocompatibility, density stability, additive compatibility, andneutrality to analyte interactions, adsorption, and leachability.

Due to the differential densities of the float 42 and the ballast 44,the mechanical separator 40 includes a center of mass R that is offsetfrom the center of volume R1 of the separator body 41. Specifically, thevolume of the separator body 41 accounted for by the float 42 may besignificantly greater than the volume of the separator body 41 accountedfor by the ballast 44. Accordingly, in certain embodiments, the centerof mass R of the separator body 41 may be offset from the through-hole46.

In accordance with another embodiment of the present invention, as shownin FIGS. 9-13, the mechanical separator 140 includes a separator body141 having a float 142 and a ballast 144 with a through-hole 146 definedwithin the float 142, as discussed above. In this configuration, shownspecifically in FIGS. 10 and 13, the first extended tab 152 and thesecond extended tab 154, taken with an upper portion 155 of the float142, form a substantially convex upper float surface 157. As shown inFIG. 9, the profile of the separator body 141 is slightly off-sphericalsuch that a diameter D₃ of the separator body extending betweendiagonally off-set endpoints 158, 159 of the through-hole 146 extendingalong the through-axis T, is slightly larger than a diameter D₄ of theseparator body extending between outermost opposing endpoints 160, 161tangent to the perimeter of the separator body 141 and perpendicular tothe through-hole 146. Accordingly, the endpoints (diagonally off-setendpoints 158, 159, and second diagonally off-set endpoints 158A, 159A)may each include a thickened area of material, such as TPE.

In accordance with another embodiment, as shown in FIGS. 14-20, themechanical separator 240 includes a separator body 241 having a float242 and a ballast 244 with a through-hole 246 defined within the float242, as discussed above. In this configuration, the through-hole 246 mayhave a substantially elliptical cross-section, as specifically shown inFIGS. 18-19. In one embodiment, the major axis M₁ of the ellipse, shownin FIG. 18, is oriented perpendicular to the through-axis T, shown inFIG. 17. By extending the major axis M₁ of the ellipse perpendicular tothe through-axis T, the float 242 may be adapted for increasedelongation in the direction of the minor axis M₂ (shown in FIG. 18) ofthe ellipse upon application of rotational force, as will be discussedherein.

In this configuration, the curvature of the first extended tab 252 andthe curvature of the second extended tab 254 are elongated tosubstantially mimic at least a portion of the elliptical first opening248 and second opening 250 of the through-axis T, respectively. Inanother embodiment, the first extended tab 252 is at least partiallycurved in shape, such as having a convex shape, and is provided adjacentthe upper portion of the first opening 248 of the through-hole 246. Thesecond extended tab 254 may also be at least partially curved in shape,such as having a convex shape, and may be provided adjacent the upperportion of the second opening 250 of the through-hole 246.

As shown in FIG. 20A, the mechanical separator 240A includes a separatorbody 241A having a float 242A and a ballast 244A with a through-hole246A defined within the float 242A, as discussed above. In thisconfiguration, the first extended tab 252A and the second extended tab254A may have an elliptical profile that is substantially coincident tothe diameter 243A of the separator body 241A at the edges of thethrough-hole 246A, and slightly offset from the diameter 243A at theapex 247A of the first and second extended tabs 252A, 254A. In thisconfiguration, the first extended tab 252A and the second extended tab254A may include enlarged fillets 280A positioned at the edges of thefirst and second extended tabs 252A, 254A adjacent the through-hole 246Ato assist in the formation of a barrier against a portion of the tubewall in the sealing position, as described herein. The enlarged fillets280A may function to facilitate the shedding of cells around themechanical separator during application of applied rotational force, asdescribed herein. The enlarged fillets 280A may also include a region ofthe first and second extended tabs 252A, 254A having an increasedthickness and/or diameter, such as a widened taper adjacent the ends ofthe first and second extended tabs 252A, 254A and extending along atleast a portion of the through-hole 246A.

As shown in FIGS. 21-22, a mechanical separator 340 of the presentinvention includes a float 342 and a ballast 344, and may include anelliptical interior 360 defining a substantially cylindricalthrough-hole 346. In this configuration, the elliptical interior 360 mayinclude a filler material 362 dimensioned to fill the ellipticalinterior 360 leaving a substantially cylindrical though-hole 346. In oneembodiment, the filler material 362 may be a TPE material or othersufficiently flexible material. Alternatively, as shown in FIGS. 23-24,a mechanical separator 440 of the present invention, including a float442 and a ballast 444, may include an elliptical interior 460 definingan elliptical through-hole 446. In yet another configuration, amechanical separator 540 of the present invention, including a float 542and a ballast 544, may include a through-hole 546 having a circularcross-section and a cylindrical shape. Optionally, the float 542 mayalso include a slit 548 or plurality of slits 548, such as adjacent aninterface 550 with the ballast 544. The inclusion of a slit 548 or aplurality of slits 548 defined within the float 542 may provide forincreased elongation of the float 542 upon application of rotationalforce, as will be discussed herein.

As shown in FIG. 27, the mechanical separator 40 of the presentinvention may be provided as a portion of a separation assembly 80 forseparating a fluid sample into first and second phases within acollection container 82 having a closure 84. Specifically, thecollection container 82 may be a sample collection tube, such as aproteomics, molecular diagnostics, chemistry sample tube, blood, orother bodily fluid collection tube, coagulation sample tube, hematologysample tube, and the like. Desirably, collection container 82 is anevacuated blood collection tube. In one embodiment, the collectioncontainer 82 may contain additional additives as required for particulartesting procedures, such as protease inhibitors, clotting agents, andthe like. Such additives may be in particle or liquid form and may besprayed onto the cylindrical sidewall 86 of the collection container 82or located at the bottom of the collection container 82. The collectioncontainer 82 includes a closed bottom end 88, an open top end 90, and acylindrical sidewall 92 extending therebetween. The cylindrical sidewall92 includes an inner surface 94 with an inside diameter extendingsubstantially uniformly from the open top end 90 to a locationsubstantially adjacent the closed bottom end 88 along the longitudinalaxis L of the collection container 82.

The collection container 82 may be made of one or more than one of thefollowing representative materials: polypropylene, polyethyleneterephthalate (PET), glass, or combinations thereof. The collectioncontainer 82 can include a single wall or multiple wall configurations.Additionally, the collection container 82 may be constructed in anypractical size for obtaining an appropriate biological sample. Forexample, the collection container 82 may be of a size similar toconventional large volume tubes, small volume tubes, or microtainertubes, as is known in the art. In one particular embodiment, thecollection container 82 may be a standard 13 ml evacuated bloodcollection tube, as is also known in the art.

The open top end 90 is structured to at least partially receive theclosure 84 therein to form a liquid impermeable seal. The closure 84includes a top end 96 and a bottom end 98 structured to be at leastpartially received within the collection container 82. Portions of theclosure 84 adjacent the top end 90 define a maximum outer diameter whichexceeds the inside diameter of the collection container 82. In oneembodiment, the closure 84 includes a pierceable resealable septum 100penetrable by a needle cannula (not shown). Portions of the closure 84extending downwardly from the bottom end 98 may taper from a minordiameter which is approximately equal to, or slightly less than, theinside diameter of the collection container 82 to a major diameter thatis greater than the inside diameter of the collection container 82 atthe top end 96. Thus, the bottom end 98 of the closure 84 may be urgedinto a portion of the collection container 82 adjacent the open top end90. The inherent resiliency of closure 84 can insure a sealingengagement with the inner surface 94 of the cylindrical sidewall 86 ofthe collection container 82. In one embodiment, the closure 84 can beformed of a unitarily molded elastomeric material, having any suitablesize and dimensions to provide sealing engagement with the collectioncontainer 82. Optionally, the closure 84 may be at least partiallysurrounded by a shield, such as a Hemogard® Shield commerciallyavailable from Becton, Dickinson and Company.

As shown in FIG. 27, the mechanical separator 40 of the presentinvention may be oriented within the collection container 82 in aninitial position in which the through-hole 46 of the mechanicalseparator 40 is aligned with the open top end 90 of the collectioncontainer 82. In the initial position, the through-hole 46 is adaptedfor allowing fluid to pass therethrough, such as from a needle cannula(not shown) which has pierced the pierceable septum 100 of the closure84 and is provided in fluid communication with the interior of thecollection container 82. The mechanical separator 40 may also bereleasably engaged with a portion of the closure 84 such that theseparator body 41 may transition from the initial position, as shown inFIGS. 27-28, to a sealing position, as shown in FIG. 29. In the initialposition, the through-hole 46 is oriented in an open position forallowing fluid to pass therethrough in the direction indicated in FIG.28 by flow arrow F. Referring to FIG. 27, the initial open position ofthe through-hole 46 is substantially aligned with the longitudinal axisL of the collection container 82. Referring to FIG. 29, upon applicationof rotational force, such as during centrifuge, the mechanical separator40 deforms sufficiently to disengage from engagement with the closure 84and rotate in the direction shown by directional arrow D of FIG. 29 tothe sealing position in which the through-hole 46 is in a substantiallyclosed position. In the substantially closed position, the float 42including the first extended tab 52 and the second extended tab 54 forma sealing engagement with the inner surface 94 of the collectioncontainer 82 substantially preventing fluid from being received throughthe through-hole 46 or around the separator body 41.

In one configuration, the through-hole 46 is substantially aligned withthe open top end 90 of the collection container 82 along at least aportion of the longitudinal axis L in the open position, and thethrough-hole 46 is substantially aligned perpendicular to thelongitudinal axis in the closed position. It is noted that transition ofthe through-hole 46 from the open position to the closed positioncoincides with the rotation of the mechanical separator 40 from a firstinitial position to a second closed position. In another configuration,the mechanical separator 40 is engaged with a portion of the closure 84in the first initial position, and the mechanical separator 40 isengaged with a portion of the sidewall 86 of the collection container 82in the second sealing position. Referring again to FIG. 27, the closure84 may include an engagement boss 102 for engagement with the mechanicalseparator 40. In one configuration, the engagement boss 102 is disposedwithin a portion of the through-hole 46 when the separator body 41 is inthe first initial position for forming a fluid seal between a portion ofthe separator body 41 and the closure 84.

In the initial position, the mechanical separator 40 may be attached tothe closure 84 be means of a mechanical snap created by an undercut inthe through-hole 46 which controls the release load of the mechanicalseparator 40. When the mechanical separator 40 is attached to theclosure 84, it forms a seal with the sidewall 86 of the collectioncontainer 82 along a first sealing perimeter 104 as shown in FIG. 30.During specimen draw into the collection container 82, the first sealingperimeter 104 prevents the accumulation of blood between the mechanicalseparator 40 and the closure 84. This reduces the formation of clotsand/or fibrin strands which may disrupt function of the mechanicalseparator 40. Upon application of rotational force and transition of themechanical separator 40 as shown in FIG. 29, the mechanical separator 40experiences a rotational moment while still attached to the closure 84and, after release from the closure 84, rotates approximately 90° tobecome oriented with the ballast 44 facing the bottom end 88 of thecollection container 82.

Once the mechanical separator 40 contacts the fluid contained within thecollection container 82, air that occupies the through-hole 46 isprogressively displaced by the fluid as the device submerges. When themechanical separator 40 is submerged in the fluid, the float 42 has agreater buoyancy than the ballast 44, which generates a differentialforce across the mechanical separator. During centrifugation, thedifferential force causes the float 42 component to elongate andcontract away from the sidewall 86 of the collection container 82,thereby reducing the effective diameter and opening a communicativepathway for the flow of fluid, such as higher and lower density phasecomponents, past the separator body 41. It is noted that the float 42may be adapted for deformation in a direction substantiallyperpendicular to the through-hole 46. As the applied rotational force isremoved, the float 42 recovers and the sealing area defined by the float42 and the first extended tab 52 and the second extended tab 54re-expands to seal against the inner surface 94 of the collectioncontainer along a second sealing perimeter 106, as shown in FIG. 31.Accordingly, the mechanical separator 40 is adapted to prevent fluidfrom passing between or around the separator body 41 and the collectioncontainer 82, and also prevents fluid from passing through thethrough-hole 46, effectively establishing a barrier. The second sealingperimeter 106 establishes a barrier between higher and lower densityphases within the sample.

As shown in FIGS. 31A-31B, the mechanical separator 140A includes aseparator body 141A having a float 142A and a ballast 144A with athrough-hole 146A defined within the float 142A, as discussed above. Inthis configuration, the float 142A may include a partially scallopedregion 150A for providing a surface to improve surface shedding ofdebris during use. As discussed herein, when the separator 140A issubmerged within a fluid sample, such as blood, certain bloodconstituents, such as fibrin or cells, may adhere to or become otherwisetrapped on the upper surface of the float 142A. In accordance with thepresent embodiment, the float 142A may include a scalloped region 150Afor increasing the surface shedding. In another embodiment, the float142A may include opposing scalloped regions 150A, such as shown in FIG.31B. The scalloped region 150A may include any curved shape suitable toincrease the surface shedding of the float, such as elliptical, oval,curved, and the like.

In this configuration, the separator body 141A may also include thefirst extended tab 152A and the second extended tab 154A having enlargedfillets 180A positioned at the edges of the first and second extendedtabs 152A, 154A adjacent the through-hole 146A to assist in theformation of a barrier against a portion of the tube wall in the sealingposition, as described herein. The enlarged fillets 180A may include aregion of the first and second extended tabs 152A, 154A having anincreased thickness and/or diameter, such as a widened taper adjacentthe ends of the first and second extended tabs 152A, 154A and extendingalong at least a portion of the through-hole 146A. In one configuration,the enlarged fillets 180A may facilitate shedding of cells around themechanical separator body 141A during application of applied rotationalforce, as described herein.

In accordance with a further embodiment of the present application, asshown in FIGS. 31C-31I, the mechanical separator 40D includes aseparator body 41D having a float 42D and a ballast 44D with athrough-hole 46D defined within the float 42D, as discussed above. Inthis configuration, the separator body 41D may have a substantiallyegg-shaped outer perimeter for improving the barrier seal between themechanical separator 40D and the sidewall of the collection container inthe sealing position, such as is shown in FIGS. 29 and 68.

In this configuration, the diameter D⁵ of the separator body 41D,specifically the float 42D as shown in FIGS. 31D and 31G, taken acrossthe float 42D in the direction along the through-axis T_(axis) of thethrough hole 46D, as shown in FIG. 31F, may be less than the diameter D₆of the separator body 41D, specifically the float 42D as shown in FIG.31D, taken across the float 42D in the direction perpendicular to thethrough-axis T_(axis) of the through hole 46D, as shown in FIG. 31F. Inthis configuration, the diameter D₇ of the separator body 41D,specifically the float 42D as shown in FIG. 31D, taken across the float42D at an angle of 45° to the through-axis T_(axis) may be larger thanthe through-hole 46D, or may be greater than the diameters D₅ and D₆ ofthe separator body 41D. Also in this configuration, the diameter D₈ ofthe ballast 44D taken across the ballast 44D along the through-axisT_(axis) of the through-hole 46D, as shown in FIG. 31F, may be less thanany of the diameters D₅, D₆, or D₇ of the separator body 41D.

The provision of a float 42D having an increased diameter with respectto the ballast 44D may provide for a mechanical separator 40D having anincreased volume of lower density material, such as TPE, for displacingagainst a sealing surface as described herein. This embodiment may alsoinclude an extended tab band, as discussed below with respect to FIGS.35A-35E, and/or an initial engagement band, as discussed below withrespect to FIGS. 33-35.

Referring to FIGS. 32-35, in a further configuration, the mechanicalseparator 40 may further include an initial engagement band 116circumferentially disposed about the separator body 41. In a furtherconfiguration, the initial engagement band 116 may be disposed about theseparator body 41 in a direction substantially perpendicular to thethrough-hole 46. The initial engagement band 116 may be continuouslyprovided about the separator body 41, or may optionally be provided insegments about the separator body 41. In yet a further configuration,the float 42 and the initial engagement band 116 may be formed from thesame material, such as TPE. The initial engagement band 116 may beprovided such that a first portion 42A of the float 42 forms the initialengagement band 116, and a second portion 42B substantially bisects theballast 44.

As shown specifically in FIG. 35, the initial engagement band 116provides an interference engagement between the separator body 41 andthe inner surface 94 of the collection container 82. In thisconfiguration, a first sealing perimeter 104 about the separator body 41is inline with the initial engagement band 116. This first sealingperimeter 104 assists in maintaining the separator body 41 in properalignment with the open top end 90 of the collection container 82, suchthat fluid entering the collection container 82 from a cannula (notshown) disposed through the pierceable septum 100 will pass through thefirst opening 48 of the separator body 41, through the through-hole 46,and out the second opening 50.

In accordance with yet another embodiment of the present invention, asshown in FIGS. 35A-35E, the mechanical separator 40C includes aseparator body 41C having a float 42C and a ballast 44C. The separatorbody 41C includes a through-hole 46C defined therein, such as definedentirely within the float 42C. In this configuration, the float 42C mayinclude an extended tab band 50C disposed about an outer surface 52C ofthe float 42C. In one embodiment, the extended tab band 50C may includea first extended portion 54C adjacent a first opening 56C of thethrough-hole 46C, and a second extended portion 58C adjacent the secondopening 60C of the through-hole 46C. In this configuration, the firstextended portion 54C and the second extended portion 58C may be providedsubstantially adjacent to at least a portion of the first opening 56Cand the second opening 60C, respectively. The first extended portion 54Cand the second extended portion 58C may each have a generally concavedownwardly-directed orientation.

The first extended portion 54C and the second extended portion 58C mayalso be provided substantially about a portion of the through-hole 46C,such as in an outwardly-extending arcuate shape about an upper portionof the through-hole 46C. A portion of the first extended portion 54C anda portion of the second extended portion 58C may extend outwardly fromthe float 42C in a direction substantially parallel to the through axisTA of the separator body 41C, such that the first extended portion 54Cand the second extended portion 58C may have substantially the sameshape and curvature.

The extended tab band 50C may also include joining portions 62C disposedbetween and connecting the first extended portion 54C and the secondextended portion 58C on both sides of the separator body 41C. Thejoining portions 62C may each have a generally concave upwardly-directedorientation. In one embodiment, the joining portions 62C, the firstextended portion 54C, and the second extended portion 58C are continuoustherewith, forming a generally “rope-like” appearance wrapped around aportion of the float 42C. In a further embodiment, the joining portions62C, the first extended portion 54C, and the second extended portion 58Cform a continuous sine function shape about a portion of the outersurface 52C of the float 42C. In another embodiment, the extended tabband 50C may be co-formed with the float 42C, forming a portion of thefloat 42C itself. In an alternative embodiment, the extended tab band50C may be separately formed and subsequently joined with the float 42C.In certain configurations, both the float 42C and the extended tab band50C are made of a lower density material, such as TPE, and the ballast44C may be formed of a higher density material, such as PET.

In one embodiment, shown specifically in FIGS. 35C and 35C1, the joiningportions 62C may each have approximately the same thickness T_(J). Inanother embodiment, the first extended portion 54C and the secondextended portion 58C may also have approximately the same thicknessT_(J). The cross-section of the extended tab band 50C may have anysuitable sealing shape such as rounded, squared, ribbed, or the like. Itis also contemplated herein, that multiple extended tab bands 50C may bedisposed about the outer surface 52C of the float 42C. Referring toFIGS. 35B and 35D, the first extended portion 54C and the secondextended portion 58C may include a thickened shelf region, 54C1 and58C1, respectively, defining a generally spline or saddle shape with theupper portion 64C of the float 42C. The upper portion 64C of the float42C and the extended tab band 50C may be particularly configured tomaximize the surface shedding of debris during use. As discussed herein,when the separator 40C is submerged within a fluid sample, such asblood, certain blood constituents, such as fibrin or cells, may adhereto or become otherwise trapped on the upper surface of the float 42C.The specific shaping of the extended tab band 50C is intended tominimize the trapping of debris during use.

In yet another embodiment, as shown in FIG. 35E, the extended tab band50C may include a first extended portion 54C, a second extended portion58C, and joining portions 62C connecting the first extended portion 54Cand the second extended portion 58C on both sides of the float 42C so asto form a continuous structure about the outer surface 52C of the float42C. In this configuration, the thickened shelf region 54C1 of the firstextended portion 54C and the thickened shelf region 58C1 of the secondextended portion 58C have a truncated profile 54C2 and 58C2,respectively, to improve surface shedding of debris during use and toprovide additional structural support to the first extended portion 54Cand the second extended portion 58C during sealing with a collectioncontainer (not shown) in the sealing position.

When the mechanical separator 40C of the present embodiment is in use,the extended tab band 50C provides a robust sealing surface against aportion of the collection container wall (not shown), similar to theseal defined by the first extended tab and the second extended tabdescribed above with reference to FIGS. 1-8. In certain embodiments, theextended tab band 50C may provide additional sealing and minimizeleakage between the mechanical separator 40C and the collectioncontainer. In addition, in the configurations in which the float 42C isformed of TPE, the extended tab band 50C provides a mechanism forenhanced sealing in that TPE does not appreciably deform underconventional applied rotational forces but rather displaces to anotherlocation. The location of the arcuate extended tab band 50C about anouter surface 52C of the float 42C allows for the TPE to displaceuniformly against a sidewall of the collection container in a sealingposition, as described herein. As the extended tab band 50C may beprovided in an alternating concave upwardly-directed and concavedownwardly-directed orientation, the sealing surface of the mechanicalseparator 40C may be located at various heights about the outer surface52C of the float 42C corresponding to the location of the extended tabband 50C.

In an additional configuration, it is intended herein that themechanical separator 40C having an extended tab band 50C may be suitablefor use in collection containers having a tilted orientation due to theenhanced sealing between the extended tab band 50C and the collectioncontainer (as described above) in the sealing position. It is alsointended herein that the mechanical separator 40C may include an initialengagement band 116, as similarly described with reference to FIG. 35above.

In accordance with yet another embodiment of the present invention, asshown in FIGS. 35F-35G, the mechanical separator 40A includes aseparator body 41A having a float 42A and a ballast 44A. The separatorbody 41A includes a through-hole 46A defined therein. In thisconfiguration, the ballast 44A may include a base portion 52A and ajoining structure 48A, such as a plurality of arms 50A for engaging aportion of the float 42A. The ballast 44A, specifically the joiningstructure 48A, may be provided in permanent engagement with a portion ofthe float 42A, such as by co-molding, two-shot molding, welding, orother adhesive joining means. In one configuration, the float 42A may beformed of a lower density material, such as TPE, and the ballast 44A maybe formed of a higher density material, such as PET. In a furtherconfiguration, the mechanical separator 40A may be dimensioned such thatthe overall density of the separator body 41A is between the density ofhigher and lower density constituents of a blood sample, such as serumand red blood cells. In yet a further embodiment, the overall density ofthe separator body 41A is 1.45 g/cm³.

As shown in FIG. 35H, the ballast 44A may include a base portion 52Ahaving a contact surface 54A and a joining surface 56A. In oneconfiguration, the contact surface 54A may include an at least partiallycurved surface 58A corresponding to an inner curvature of a collectioncontainer (not shown). The joining surface 56A may include an attachmentbetween the base portion 52A and the joining structure 48A. In oneconfiguration, the joining surface 56A and the joining structure 48A areco-formed. In another configuration, the joining surface 56A and thejoining structure 48A are separately formed and subsequently provided inpermanent attachment through mechanical or adhesive locking means.

The joining structure 48A may include a first end 60A for engaging thebase portion 52A of the ballast 44A and a second end 62A for engaging aportion of the float 42A. The top view of the float 42A may have asubstantially circular outer perimeter P_(o), as shown in FIG. 35I, andthe float 42A may have a substantially curved cross-sectional side view,such as a substantially concave down cross-section as shown in FIG. 35H.In a further embodiment, the float 42A may have a substantially concavedown cross-section adjacent an apex 64A of the float 42A, and a slightconcave upward curvature adjacent the perimeter P_(o) of the float 42A,such as at a location at which the second end 62A of the joiningstructure 48A is attached to the float 42A. In one configuration, thesecond end 62A of the joining structure 48A is molded first and thefloat 42A is subsequently molded onto the second end 62A of the joiningstructure 48A to form a bond therewith. In another embodiment, thesecond end 62A of the joining structure 48A is inserted within, orprovided adjacent to, a portion of the float 42A and subsequently bondedor otherwise adhered thereto.

In one configuration, the joining structure 48A may provide flexurebetween the float 42A and the base portion 52A. The flexure may beprovided by at least one of the attachment between the first end 60A ofthe joining structure 48A and the base portion 52A, the attachmentbetween the second end 62A of the joining structure 48A and the float42A, and the pivot points 68A of the joining structure 48A.

Referring to FIG. 35J, the mechanical separator 40A may be providedwithin a collection container 100A, such as adjacent an upper end 102Aof the collection container 100A in an initial position. The mechanicalseparator 40A may be provided in engagement with a portion of a stopper104A, such that a portion of the stopper 104A extends through thethrough-hole 46A of the mechanical separator 40A, as described elsewhereherein. In accordance with another embodiment of the present invention,the mechanical separator 40A may be provided such that a portion of thefloat 42A and a portion of the base portion 52A of the ballast 44Aengage an inner surface of the collection container 100A to restrain themechanical separator 40A within the upper end 102A of the collectioncontainer 100A such that the through-hole 46A of the mechanicalseparator 40A is aligned with the longitudinal axis L_(A) of thecollection container 100A.

Referring again to FIG. 35J, a fluid specimen 108A, such as blood, isintroduced into the collection container 100A, such as through thestopper 104A and aligned with through-hole 46A of the mechanicalseparator 40A when the mechanical separator 40A is oriented in theinitial position as shown by reference character A. As rotational forceis applied, the float 42A flexes and initiates a flexure between thefloat 42A and the ballast 44A, as described above. The resulting flexuredeforms the through-hole 46A and the mechanical separator 40A disengagesfrom the stopper 104A and begins to rotate in the direction shown byarrow R, as shown by reference character B.

As the mechanical separator 40A becomes submerged within the fluidspecimen 108A, the float 42A begins to orient in an upward direction andthe ballast 44A simultaneously begins to orient in a downwardsdirection, as shown by reference character C. During the continuedapplication of rotational force, the ballast 44A pulls in a downwardsdirection and the float 42A flexes away from the sidewall 110A of thecollection container, as shown by reference character D. Subsequently,as shown by reference character E, the float 42A is deformed to allowfor the passage of higher and lower density phase constituents betweenthe float 42A and the sidewall 110A of the collection container 100A.This allows for separation of the higher and lower density phaseconstituents within the fluid sample 108A, as well as for the separationof higher and lower density phase constituents within the fluid sample108A present within the through-hole 46A of the mechanical separator40A.

Referring to FIG. 35K, once the application of rotational force hasceased, the mechanical separator 40A becomes oriented between theseparated higher density phase 112A and the separated lower densityphase 114A in a sealing position. At the same time, the flexure betweenthe float 42A and the ballast 44A ceases, causing the float 42A toreturn to its initial position, as shown in FIG. 35I, thereby forming aseal between the outer perimeter P_(o) and the interior circumference ofthe sidewall 110A of the collection container 100A. The float 42A has anouter perimeter P_(o) having an outer circumference that is at leastslightly larger than the interior circumference of the sidewall 110A ofthe collection container 100A, thereby forming a robust sealtherebetween.

Referring yet again to FIG. 35K, once the mechanical separator 40A hasbeen transitioned to the sealing position, a sealing perimeter isestablished along the outer perimeter P_(o) between at least a portionof the interior circumference of the sidewall 110A and the mechanicalseparator 40A. As shown in FIG. 35K, the sealing perimeter along theouter perimeter P_(o) has a varying position about the interiorcircumference of the sidewall 110A as measured from the closed bottomend 113A of the collection container 100A. In one configuration, thesealing perimeter along the outer perimeter P_(o) includes varioussealing heights at each localized sealing location, S₁, S₂, S₃, etc.corresponding to the overall height of the seal between the mechanicalseparator 40A, specifically, the float 42A, and the sidewall 110A. Thesealing perimeter accordingly has a height which varies slightly at eachlocalized sealing location S₁, S₂, S₃, etc. The sealing perimeter alsodefines an average sealing height H_(Avg) which corresponds to theaverage height of each localized sealing location S₁, S₂, S₃, etc.,i.e., H_(Avg)=Avg [S₁, S₂, S₃, etc.]. The mechanical separator 40A alsohas a maximum height H_(Max) and a minimum height H_(Min) within thecollection container. The maximum height H_(Max) corresponds to thedistance between the highest seal point along the outer perimeter P_(o)and the closed bottom end 113A of the collection container 100A. Theminimum height H_(Min) corresponds to the lowest seal point along theouter perimeter P_(o) and the closed bottom end 113A of the collectioncontainer 100A. In accordance with an aspect of the present invention,the average sealing height H_(Avg) is less than the difference betweenthe maximum seal height H_(Max) and the minimum seal height H_(Min),i.e., H_(Avg)<H_(Max)−H_(Min).

In accordance with another embodiment of the present invention, as shownin FIGS. 35L-35M, the mechanical separator 40B includes a separator body41B having a float 42B and a ballast 44B. The separator body 41Bincludes a through-hole 46B defined therein. In this configuration, thefloat 42B may include a joining structure 48B, such as a plurality ofarms 50B for engaging a portion of the ballast 44B. As similarlydescribed above, the joining structure 48B may be provided in permanentengagement with a portion of the ballast 44B, such as by co-molding,two-shot molding, welding, or other adhesive joining means. In thisconfiguration, the joining structure 48B may exhibit increasedflexibility allowing for easier transition from an initial position to asealing position, as described herein.

Referring again to FIGS. 35L-35M, in one configuration, the float 42Bmay include a cut-out 60B within the float 42B. In one embodiment, thecut-out 60B may be positioned at the apex 62B of the float 42B and doesnot extend into the outer perimeter P_(o). The cut-out 60B may providefor increased flexibility to allow passage of higher and lower densityphase constituents thereby during use, such as shown in FIG. 35J withreference to reference character E. In yet a further configuration, thejoining structure 48B may include an opening 64B therein adapted toallow a portion of the ballast 44B to pass therethrough and be securedtherein, such as by way of a mechanical interlock. In one embodiment,the joining structure 48B includes a continuous arm 50B connected to thefloat 42B at a first end 68B and a second end 70B. The joining structure48B may include an opening 64B having a locking portion 72B of theballast 44B extending therethrough. In one embodiment, the opening 64Bmay be disposed within the continuous arm 50B at a location opposed fromthe apex 62B of the float 42B. In another embodiment, the ballast 44B,such as the locking portion 72B, and the float 42B may be provided inpermanent engagement so as to minimize separation of the float 42B andthe ballast 44B.

Referring to FIGS. 35N-35O, in a further embodiment of the presentinvention, the mechanical separator 40B includes a separator body 41Bhaving a float 42B and a ballast 44B. The separator body 41B includes athrough-hole 46B defined therein. In this configuration, the float 42Bmay include a joining structure 48B, such as a plurality of arms 50B forengaging a portion of the ballast 44B. As similarly described above, thejoining structure 48B may include a continuous arm 50B connected to thefloat 42B at a first end 68B and a second end 70B. The joining structure48B may include an opening 64B having a locking portion 72B of theballast 44B extending therethrough in permanent engagement so as tominimize separation of the float 42B and the ballast 44B. The ballast44B may also include a support structure 74B adjacent and connected tothe joining structure 48B of the float 42B. In one embodiment, thesupport structure 74B of the ballast 44B may be co-formed or otherwisepermanently engaged with the joining structure 48B of the float 42B. Ina further embodiment, the joining structure 48B may define a recessadapted to at least partially surround the support structure 74B. In yeta further embodiment, the support structure 74B and the joiningstructure 48B allow the float 42B and ballast 44B to at least partiallyflex with respect to each other, as described herein. In certainconfigurations, a ballast cut-out 80B may be provided within the baseportion 52B to lessen shrinkage of the ballast 44B during formation.

Although the through-hole of the mechanical separator of the presentinvention has been shown herein as a straight bore having a spherical orelliptical cross-section, it is also contemplated herein that thethrough-hole 546, as shown in FIGS. 36-37, may define a serpentine orcircuitous path for receiving liquid therethrough. In thisconfiguration, the mechanical separator 540 includes a through-hole 546having a first opening 549 and a second opening 551 that are offset withrespect to each other. Specifically, the first opening 549 and thesecond opening 551 may be offset, such as at 60° or 90° angles withrespect to each other. As shown in FIG. 36, in the initial position, thefirst opening 549 is aligned with the top open end 590 of the collectioncontainer 582, represented herein in section. Fluid is directed throughthe through-hole 546 in the direction as shown by directional arrow R.In this configuration, at least one surface of the second opening 551contacts the sidewall of the collection container 582, while anothersurface of the second opening 551 remains free within the interior ofthe collection container 582. Accordingly, a gap is provided between thesidewall of the collection container 582 and the second opening 551 ofthe through-hole 546 to allow fluid to exit the through-hole 546 andpass into the interior of the collection container 582.

Upon application of rotational force, the mechanical separator 540 willtransition from the initial position, as shown in FIG. 36, to a sealingposition, as shown in FIG. 37, along directional arrow S, due to themoment of the float and ballast components as described herein. In thisconfiguration, both the first opening 549 and the second opening 551 ofthe through-hole 546 are provided out of alignment with the top open end590 of the collection container 582 and are adapted such that fluid isnot directed into the through-hole 546. A second sealing perimeter 595is also established about the mechanical separator 540 such that fluidcannot pass between the mechanical separator 540 and the collectioncontainer 582 or through the through-hole 546 of the mechanicalseparator 540, effectively establishing a barrier.

In yet another configuration, as shown in FIGS. 38-39, the elongation ofthe mechanical separator 640 during application of rotational force isexemplified. In this configuration, the mechanical separator 640 mayinclude a float 642 and a ballast 644 with a third section 643 joiningthe float 642 and the ballast 644. It is contemplated herein, that inthis configuration, both the float 642 and the ballast 644 may be madeof a substantially rigid material with the float 642 having a densitythat is less than the density of the ballast 644. In order to providefor an elongation between these components, the third section 643 formedof a flexible material, such as TPE, may be provided therebetween.During centrifugation, the third section 643 elongates, as shown in FIG.39, in a manner similarly described with respect to the elongation ofthe float above. During elongation of the third section 643, higher andlower density phases of a fluid may pass adjacent the fluid passagesurfaces 645, as shown in FIG. 39 as in a direction extending into thepage.

With reference again to FIG. 2 and FIGS. 40 and 41, the separator body41 may include a center of mass R that is offset from the through-axisT, shown in FIG. 2, of the separator body 41. In this configuration, themechanical separator 40 is transitionable from a first position (such asshown in FIGS. 40-41) in which the mechanical separator 40 is engagedwith a portion of the closure 84 (shown in FIG. 41) or a portion of thesidewall 86 of the collection container 82 (shown in FIG. 40) and thecenter of mass R is oriented on a first side S₁ of the longitudinal axisL of the collection container 82, to a second position, such as shown inFIG. 29, in which the mechanical separator 40 is disengaged from theclosure or initial engagement position with the collection container,and the center of mass R is oriented across the longitudinal axis L ofthe collection container 82. At some point, during the transition of thecenter of mass R across the longitudinal axis L of the collectioncontainer 82, the float 42 of the mechanical separator 40 must deform ina direction substantially perpendicular to the through-axis T of theseparator body 41 in order to allow for transition of the mechanicalseparator 40 from the initial first position to the second sealingposition. During elongation of the float 42, the higher and lowerdensity phases of the specimen may pass between the mechanical separator40, specifically the elongated float 42, and the sidewall 86 of thecollection container 82 in which the mechanical separator is in anintermediate position. From the intermediate position, the mechanicalseparator may subsequently transition to the sealing position, in whicha portion of the float 42 forms a sealing engagement with a portion ofthe interior of the collection container, upon termination of appliedrotational force.

Accordingly, the mechanical separator of the present invention may beconsidered to transition between three phases of operation: the initialphase in which a specimen is provided through the through-hole of theseparator body; the intermediate phase in which the separator hasdisengaged from the initial position and the float 42 is elongated toallow passage of higher and lower density phases thereby; and thesealing position in which the float 42 forms a barrier with a portion ofthe collection container. During this sequence of phases, the mechanicalseparator may be considered as “open-open-closed” wherein an “open”phase is defined as a state in which the mechanical separator does notform a sealing barrier with the collection container preventing thepassage of fluid therethrough and therearound. In contrast, a “closed”phase is defined as a state in which mechanical separator 40 does form asealing barrier with the collection container preventing the passage offluid therethrough and therearound.

The mechanical separator of the present invention is also intended foruse with various closure arrangements in the initial phase. Referring toFIG. 40, the mechanical separator 40 may be maintained in the initialposition by the interference between the float 42 and the initialengagement band 116 and the sidewall 86 of the collection container 82.In this configuration, the mechanical separator 40 is not restrained byany portion of the closure 84.

In another configuration, as shown in FIGS. 41-44, the separationassembly includes a closure 84 and a post 180 engaged within a recess181 of the closure 84. The post 180 may include a separator receivingend 182 and a closure engagement end 183. The closure engagement end 183may be adapted for positioning within the recess 181 of the closure 84and may optionally include at least one barb 184 for securing the post180 within the closure 84. The separator receiving end 182 may have anysuitable profile such that it may be at least partially disposed withinthe through-hole 46 of the separator body 41. In one embodiment, theseparator receiving end 182 has a substantially circular cross-section.In another embodiment, the separator receiving end 182 has asubstantially elliptical cross-section. The separator receiving end 182is dimensioned to snugly fit within the through-hole 46 to provide areleaseable engagement with the mechanical separator 40. The post 180 isalso adapted for positioning within the interior of the collectioncontainer 82 and includes a post through-hole 186 aligned along thelongitudinal axis of the collection container 82. When the mechanicalseparator 40 is engaged with the post 180, a fluid path is formedbetween the through-hole 46 of the mechanical separator 40 and the postthrough-hole 186 of the post 180. This effectively forms a “sealed”fluid path for the direction of the fluid sample into the collectioncontainer 82. Upon application of rotational force, the mechanicalseparator experiences a slight longitudinal movement prior to the axialrotation as the mechanical separator is pulled downward off the post 180during applied rotation.

Referring to FIGS. 45-46, an alternative separation assembly is shownincluding a collection container 782 having a first region 783 having anopen top end 784 and a first sidewall 785 defining a first interior 786and a first exterior 787. The collection container 782 also includes asecond region 788 having a closed bottom end 789 and a second sidewall790 defining a second interior 791 and a second exterior 792. In thisconfiguration, the first region 783 and the second region 788 arealigned along a longitudinal axis L_(A) such that the first interior 786and the second interior 791 are provided in fluid communication. Thefirst interior 786 includes a first diameter D_(F) and the secondinterior 791 includes a second diameter D_(S), with the first diameterD_(F) being greater than the second diameter D_(S). The collectioncontainer 782 also includes at least one fluid flute 793 extendingbetween the first region 783 and the second region 788 to allow passageof fluid therethrough from the first region 783 to the second region788. In this configuration, the first exterior 787 of the first region783 may have a profile that corresponds to a 16 mm collection tube, andthe second exterior 792 of the second region 788 may have a profile thatcorresponds to a 13 mm collection tube.

The first interior 786 of the first region 783 may be dimensioned toaccommodate a mechanical separator 40 therein in any of theconfigurations described herein. The second interior 791 is dimensionedto at least partially restrain a portion of the mechanical separator 40from passing therein in the initial position and absent appliedrotational force. During application of rotational force, the floatportion 42 of the mechanical separator 40 may elongate therebydecreasing the effective diameter of the mechanical separator 40 andallowing passage of the mechanical separator into the second interior791. In this configuration, the orientation of the through-hole 46 ofthe mechanical separator 40 is irrelevant as the introduction of fluidsample into the collection container 782 occurs around the separatorbody 41 as opposed to through the through-hole 46. Specifically, fluidis introduced into the collection container 782 into the first interior786 and around the mechanical separator 40. The sample then passes intothe second interior 791 by way of the fluid flutes 793. Accordingly, theinitial orientation of the mechanical separator 40 is irrelevant to thefunction of the separator in this embodiment.

In accordance with a further embodiment of the present invention, asshown in FIG. 46A, a mechanical separator, as described herein, may beused with a collection container 782A having a slight taper along aportion of the sidewall 783A extending between an open top end 784A anda closed bottom end 785A. In this configuration, the collectioncontainer 782A includes a first region indicator section A of FIG. 46A.First region indicator section A is disposed along a portion of thesidewall 783A at a distance 786A from the open top end 784A. Thecollection container 782A may also include a second region indicatorsection B of FIG. 46A. Second region indicator section B is disposedalong a portion of the sidewall 783 at a distance 788A from the open topend 784A. In one configuration, the region defined between the firstregion indicator section A and the second region indicator B may havesubstantially no taper. In another configuration, the region definedbetween the first region indicator section A and the second regionindicator B may have substantially may have a slight inward taper. In afurther embodiment, the region defined between the first regionindicator section A and the second region indicator B may be about theexpected separation transition between the separated higher and lowerdensity phases of a liquid to be separated.

In yet another embodiment, shown in FIGS. 47-48, the separation assemblyincludes a closure 850 adapted for sealing engagement with thecollection container 852. The closure 850 includes a receiving end 842for positioning within the open end 853 of the collection container 852.The receiving end 842 defines an interior cavity 854 and includes anundercut protrusion 855 extending into the interior cavity 854. Theundercut protrusion 855 of the closure 850 is at least partiallydisposed within the through-hole 46 of the mechanical separator 40 inthe initial position. Also in the initial position, at least a portionof the separator body 41 is disposed within the interior cavity 854. Thepositioning of the mechanical separator 40 within the interior cavity854 ensures that the mechanical separator 40 remains captured in theclosure 850 during assembly of the closure 850 with the collectioncontainer 852. This configuration may be utilized with the collectioncontainer having a first region and a second region, as described above.During application of rotational force, the float 42 of the mechanicalseparator 40 elongates allowing the mechanical separator 40 to disengagefrom the closure 850.

Referring now to FIGS. 49-59, various other engagements between themechanical separator 40 and the closure 84 are also contemplated herein.As shown in FIG. 49, the mechanical separator 40 may include an angledengagement boss 900 disposed within the through-hole 46 in the initialposition. As shown in FIG. 50, the mechanical separator 40 may include asubstantially cylindrical engagement boss 901 disposed within thethrough-hole 46 in the initial position. A flanking portion 902 of theclosure 903 may be provided adjacent an exterior surface 904 of themechanical separator 40 adjacent the first opening 905 for furthersecuring the mechanical separator 40 with the closure 903 andestablishing a “sealed” fluid path into the collection container 906therethrough.

Referring to FIGS. 51-52, a sealant 907 may be provided adjacent theflanking portion 902, as described above, for further securing themechanical separator 40 and the closure 903. The sealant 907 may besufficiently tacky to retain the mechanical separator 40 in place in theinitial position, yet weak enough to permit release of the mechanicalseparator 40 from the closure 903 upon application of rotational force.

Referring to FIG. 53, yet another alternative angled engagement boss 908may be disposed within the through-hole 46 in the initial position.Referring to FIGS. 54-55, the closure 910 may include at least one, suchas two, depending arms 911 for engagement with the mechanical separator40. In one configuration, each depending arm 911 includes a contactprotrusion 912 for engaging a portion of the mechanical separator 40within the through-hole 46 in the initial position. The interferencebetween the contact protrusion 912 and the mechanical separator 40 maybe sufficient to restrain the mechanical separator 40 with the closure910 in the initial position, yet allow for disengagement of themechanical separator 40 from the closure 910 upon application ofrotational force.

Referring to FIGS. 56-57, the closure 915 may include a molding insert916 having a wedging basket 917 for further securing the molding insert916 with the closure 915. As described above, the molding insert 916 mayinclude a separator receiving end 918 for engaging the mechanicalseparator 40 through the through-hole 46, and a closure engagement end919, as described above. Referring to FIG. 58, another molding insert920 may include at least one barb 921 for further securing the moldinginsert 920 with the closure 922. Referring to FIG. 59, yet anothermolding insert 930 may include at least one protrusion 931 for securingthe molding insert 930 with the closure 932.

Referring to FIGS. 60-68, the separation assemblies described herein mayalso include a carrier 650 releasably engaged with a portion of themechanical separator 40 in the initial position. In each of theseconfigurations, the carrier 650 disengages from the mechanical separator40 upon application of rotational force and enters the fluid phasedisposed below the mechanical separator 40 for the purpose of preventingclots or fibrin strands from interfering with the operation of themechanical separator 40.

As shown in FIG. 60, the carrier 650 may include a closure engagementportion 651 for releasable engagement with a portion of the closure 652,and a depending portion 653 for releasable engagement with a portion ofthe mechanical separator 40, such as through the through-hole 46. Asshown in FIG. 61, the carrier 650 may include a closure engagementportion 651 having a plurality of flanges 654. The carrier 650 may alsoinclude a bowed separator engagement portion 655 for engaging a portionof the mechanical separator 40, such as within the through-hole 46. Uponapplication of rotational force, the mechanical separator 40 disengagesfrom the initial position and rotates as described herein. Upon rotationof the mechanical separator 40, the bowed separator engagement portion655 contracts and allows the mechanical separator 40 to separate fromthe carrier 650.

Referring to FIGS. 63-66, the carrier 650 may also be releasablyconnected to the mechanical separator 40 in a direction opposed from theclosure 660. Referring to FIGS. 67-68, the carrier 650 may optionallyconsist of a dissolvable material which diffuses into the sample whencontact is made, as shown in FIG. 68.

One of the significant benefits of the mechanical separator of thepresent invention is that it does not require penetration by a needlecannula in order to permit entry of a fluid sample into a collectioncontainer. In each of the above-described embodiments, when the assemblyis subjected to an applied rotational force, such as centrifugation, therespective phases of the specimen, such as blood, will begin to separateinto a denser phase displaced toward the bottom of the collectioncontainer, and a less dense phase displaced toward the top of thecollection container. The applied rotational force will urge the ballastof the mechanical separator toward the closed bottom end and the floattoward the top end of the collection container. This movement of theballast will generate a longitudinal deformation of the float. As aresult, the float will become longer and narrower and will be spacedconcentrically inward from the inner surface of the cylindrical sidewallof the collection container. Accordingly, lighter phase components ofthe blood will be able to slide past the float and travel upwards, andlikewise, heavier phase components of the blood will be able to slidepast the float and travel downwards.

As noted above, the mechanical separator of the present inventiontypically has an overall density between the densities of the separatedphases of the blood. Consequently, the mechanical separator willstabilize in a position within the collection container such that theheavier phase components will be located between the mechanicalseparator and the closed bottom end of the collection container, whilethe lighter phase components will be located between the mechanicalseparator and the top end of the collection container.

After this stabilized state has been reached, the centrifuge will bestopped and the float will resiliently return to its unbiased state andinto sealing engagement with the interior of the cylindrical sidewall ofthe collection container. The formed liquid phases may then be accessedseparately for analysis. In one embodiment, the assembled mechanicalseparator of the present invention may be scaled to fit within a 13 mmcollection tube.

In use, the mechanical separator of the present invention minimizesdevice pre-launch and eliminates the need for cannula puncture whichsubstantially eliminates sample pooling under the closure. Additionally,the reduced clearance of the mechanical separator minimizes the loss oftrapped fluid phases, such as serum and plasma.

While the present invention is described with reference to severaldistinct embodiments of a mechanical separator assembly and method ofuse, those skilled in the art may make modifications and alterationswithout departing from the scope and spirit. Accordingly, the abovedetailed description is intended to be illustrative rather thanrestrictive.

The invention claimed is:
 1. A mechanical separator for separating afluid sample into first and second phases within a collection container,comprising: a separator body having a through-hole defined therein, thethrough-hole adapted for allowing fluid to pass therethrough, theseparator body comprising: a float, having a first density; and aballast comprising a base portion having a first surface and a secondopposite surface and an extension portion connected to the base portion,the ballast having a second density greater than the first density,wherein the first surface of the base portion of the ballast isconnected to the float and the extension portion extends outwardly fromthe second opposite surface of the ballast, and wherein the through-holeis entirely defined by either the float, or the float and at least aportion of the first surface of the base portion of the ballast.
 2. Themechanical separator of claim 1, wherein at least a portion of theseparator body is adapted to resiliently deform upon application ofrotational force.
 3. The mechanical separator of claim 1, wherein theseparator body has a generally spheroid shape and an outer surface ofthe float at an interface between the float and the ballast is offsetfrom an outer surface of the ballast at the interface.
 4. The mechanicalseparator of claim 1, wherein the separator body has a generallyspheroid shape and an outer perimeter of the float at an interfacebetween the float and the ballast is offset from an outer perimeter ofthe ballast at the interface.
 5. The mechanical separator of claim 1,wherein the separator body has a center of mass and a center of volumethat is offset from the center of mass.
 6. The mechanical separator ofclaim 1, wherein the separator body has a center of mass that is offsetfrom a through-axis of the through-hole.
 7. The mechanical separator ofclaim 1, wherein the separator body has a center of volume that islocated within the through-hole.
 8. The mechanical separator of claim 1,wherein the through-hole defines a first open face at a first end of theseparator body and a second open face at a second end of the separatorbody, the first end of the separator body substantially opposite thesecond end of the separator body, the float defines a first exteriorsurface of the separator body extending from a portion of the first openface to a portion of the second open face and the ballast defines asecond exterior surface, the second exterior surface substantiallyopposite the first exterior surface and, in a plane bisecting theseparator body and extending from the first exterior surface to thesecond exterior surface and in a direction parallel to a through axis ofthe through-hole, the through-hole has a first portion where the firstopen face is a first distance from the second open face and a secondportion where the first open face is a second distance from the secondopen face, the first distance being different from the second distance.9. The mechanical separator of claim 1, wherein the float defines anupper exterior surface of the separator, the ballast defines a lowerexterior surface of the separator, and a through-axis of thethrough-hole is disposed within a plane angled with respect to a planeextending vertically from an apex of the upper exterior surface of thefloat to an apex of the lower exterior surface of the ballast andbisecting the separator into a first half and a second half, wherein thefirst half includes a first opening of the through-hole and the secondhalf includes a second opening of the through-hole, and the apex of theupper exterior surface and the apex of the lower exterior surface arealigned along a central longitudinal axis of the separator.
 10. Themechanical separator of claim 9, wherein the float has a first diameteron a first side of the through-hole which is different from a seconddiameter at an opposite second side of the through-hole and the firstand second float diameters are parallel with a through-axis of thethrough-hole.
 11. The mechanical separator of claim 1, wherein anoutermost perimeter of the body as viewed from above in a directionextending from a top surface of the body defined by the float to abottom surface of the body defined by the ballast is asymmetric about adiameter of the outermost perimeter of the body extending through acenter of the outermost perimeter.
 12. The mechanical separator of claim1, wherein an outermost perimeter of the body as viewed from above in adirection extending from a top surface of the body defined by the floatto a bottom surface of the body defined by the ballast bounds fourquadrants defined by the intersection of a first axis and a second axis,the first axis intersects and is perpendicular to the second axis at acenter of the top surface, each quadrant is bisected by an orientationaxis, a first radial distance extending from the center of the topsurface to a first contact point of the perimeter along the first axisis less than a second radial distance extending from the center of thetop surface to a second contact point of the perimeter along the secondaxis, and the first radial distance and the second radial distance areless than a third radial distance extending from the center of the topsurface to a contact point of the perimeter along one of the orientationaxes.
 13. The mechanical separator of claim 1, wherein the base portionof the ballast has a first diameter, the extension portion has a seconddiameter, and the second diameter is less than the first diameter. 14.The mechanical separator of claim 1, wherein the extension portion ofthe ballast has an exterior surface that is generally rounded.
 15. Aseparation assembly for enabling separation of a fluid sample into firstand second phases, comprising: a collection container having a firstend, a second end, and a sidewall extending therebetween, the collectioncontainer defining a longitudinal axis between the first end and thesecond end; and a separator having a through-hole defined therein, thethrough-hole adapted for allowing fluid to pass therethrough, theseparator comprising: a float, having a first density; a ballast,comprising a base portion having a first surface and a second oppositesurface and an extension portion connected to the base portion, whereinthe ballast has a second density greater than the first density; and atleast one sealing perimeter, wherein the first surface of the baseportion of the ballast is connected to the float and the extensionportion extends outwardly from the second opposite surface of theballast, and wherein the separator is adapted to transition from a firstinitial position in which the through-hole is oriented in an openposition for allowing fluid to pass therethrough to a second sealingposition in which the through-hole is oriented in a closed position forpreventing fluid from being received therethrough, upon appliedcentrifugal force, and at least a portion of the through-hole isoriented in a first orientation with respect to the longitudinal axis ofthe collection container in the first initial position, and at least aportion of the through-hole is oriented in a second orientation withrespect to the longitudinal axis of the collection container in thesecond sealing position, the second orientation being different than thefirst orientation.
 16. The separation assembly of claim 15, wherein theseparator defines a separator body and at least a portion of theseparator body is adapted to resiliently deform upon application ofrotational force.
 17. The separation assembly of claim 15, wherein, inthe second sealing position, the at least one sealing perimetersealingly engages a portion of the sidewall of the collection containerto prevent fluid from passing between the separator and the sidewall andto prevent fluid from passing through the through-hole, and at least aportion of the through-hole is oriented along the longitudinal axis ofthe collection container in the first initial position and at least aportion of the through-hole is oriented perpendicular to thelongitudinal axis of the collection container in the second sealingposition.
 18. The separation assembly of claim 15, wherein the separatorcomprises a first sealing perimeter for providing sealing engagementwith a first portion of a collection container in the first initialposition and a second sealing perimeter for providing sealing engagementwith a second portion of the collection container in the second sealingposition, wherein the through-hole is defined along a through-axis andthe first sealing perimeter and the second sealing perimeter are atdifferent angles with respect to the through-axis of the through-hole.19. The separation assembly of claim 15, wherein the separator comprisesa first sealing perimeter for providing sealing engagement with a firstportion of a collection container in the first initial position and asecond sealing perimeter for providing sealing engagement with a secondportion of the collection container in the second sealing position,wherein the first sealing perimeter is different from the second sealingperimeter.
 20. The separation assembly of claim 15, wherein, in thefirst initial position, a through-axis of the through-hole is parallelto the longitudinal axis of the collection container and in the secondsealing position, the through-hole is transverse to the longitudinalaxis of the collection container.
 21. The separation assembly of claim15, wherein the sealing perimeter has a first diameter in a directionparallel to a through-axis of the through-hole, a second diameter in adirection perpendicular to the through-axis of the through-hole, and thefirst diameter is less than the second diameter.
 22. The separationassembly of claim 15, wherein the collection container has across-section along an axis extending perpendicular to the longitudinalaxis having a first perimeter shape taken within the interior, anoutermost perimeter of the separator as viewed from above in a directionextending from a top surface of the separator to a bottom surface of theseparator has a second perimeter shape, and the second perimeter shapeis different than the first perimeter shape.
 23. The separation assemblyof claim 15, wherein the through-hole has a first open end and a secondopen end, the separator has a sealing perimeter that forms a sealbetween the separator and the sidewall of the collection container, andat least a portion of the sealing perimeter defines at least a portionof a perimeter of the first open end of the through-hole and at least aportion of the sealing perimeter defines at least a portion of aperimeter of the second open end of the through-hole.
 24. A mechanicalseparator for separating a fluid sample into first and second phaseswithin a collection container, comprising: a separator body having athrough-hole defined therein, the through-hole adapted for allowingfluid to pass therethrough, the separator body comprising: a float,having a first density; and a ballast comprising a base portion having afirst surface and a second opposite surface and an extension portionconnected to the base portion, the ballast having a second densitygreater than the first density, wherein the first surface of the baseportion of the ballast is connected to the float and the extensionportion extends outwardly from the second opposite surface of theballast, and wherein the through-hole defines a first open face at afirst end of the separator body and a second open face at a second endof the separator body, the first end of the separator body substantiallyopposite the second end of the separator body, the float defines a firstexterior surface of the separator body extending from a portion of thefirst open face to a portion of the second open face and the ballastdefines a second exterior surface, the second exterior surfacesubstantially opposite the first exterior surface and, in a planebisecting the separator body and extending from the first exteriorsurface to the second exterior surface and in a direction parallel to athrough axis of the through-hole, the through-hole has a first portionwhere the first open face is a first distance from the second open faceand a second portion where the first open face is a second distance fromthe second open face, the first distance being different from the seconddistance.
 25. A mechanical separator for separating a fluid sample intofirst and second phases within a collection container, comprising: aseparator body having a through-hole defined therein, the through-holeadapted for allowing fluid to pass therethrough, the separator bodycomprising: a float, having a first density; and a ballast comprising abase portion having a first surface and a second opposite surface and anextension portion connected to the base portion, the ballast having asecond density greater than the first density, wherein the first surfaceof the base portion of the ballast is connected to the float and theextension portion extends outwardly from the second opposite surface ofthe ballast, and wherein the float defines an upper exterior surface ofthe separator, the ballast defines a lower exterior surface of theseparator, and a through-axis of the through-hole is disposed within aplane angled with respect to a plane extending vertically from an apexof the upper exterior surface of the float to an apex of the lowerexterior surface of the ballast and bisecting the separator into a firsthalf and a second half, wherein the first half includes a first openingof the through-hole and the second half includes a second opening of thethrough-hole, and the apex of the upper exterior surface and the apex ofthe lower exterior surface are aligned along a central longitudinal axisof the separator.
 26. The mechanical separator of claim 25, wherein thefloat has a first diameter on a first side of the through-hole which isdifferent from a second diameter at an opposite second side of thethrough-hole and the first and second float diameters are parallel witha through-axis of the through-hole.
 27. A mechanical separator forseparating a fluid sample into first and second phases within acollection container, comprising: a separator body having a through-holedefined therein, the through-hole adapted for allowing fluid to passtherethrough, the separator body comprising: a float, having a firstdensity; and a ballast comprising a base portion having a first surfaceand a second opposite surface and an extension portion connected to thebase portion, the ballast having a second density greater than the firstdensity, wherein the first surface of the base portion of the ballast isconnected to the float and the extension portion extends outwardly fromthe second opposite surface of the ballast, and wherein an outermostperimeter of the body as viewed from above in a direction extending froma top surface of the body defined by the float to a bottom surface ofthe body defined by the ballast is asymmetric about a diameter of theoutermost perimeter of the body extending through a center of theoutermost perimeter.
 28. A mechanical separator for separating a fluidsample into first and second phases within a collection container,comprising: a separator body having a through-hole defined therein, thethrough-hole adapted for allowing fluid to pass therethrough, theseparator body comprising: a float, having a first density; and aballast comprising a base portion having a first surface and a secondopposite surface and an extension portion connected to the base portion,the ballast having a second density greater than the first density,wherein the first surface of the base portion of the ballast isconnected to the float and the extension portion extends outwardly fromthe second opposite surface of the ballast, and wherein an outermostperimeter of the body as viewed from above in a direction extending froma top surface of the body defined by the float to a bottom surface ofthe body defined by the ballast bounds four quadrants defined by theintersection of a first axis and a second axis, the first axisintersects and is perpendicular to the second axis at a center of thetop surface, each quadrant is bisected by an orientation axis, a firstradial distance extending from the center of the top surface to a firstcontact point of the perimeter along the first axis is less than asecond radial distance extending from the center of the top surface to asecond contact point of the perimeter along the second axis, and thefirst radial distance and the second radial distance are less than athird radial distance extending from the center of the top surface to acontact point of the perimeter along one of the orientation axes.